The general objective of this research project is to study at the membrane level changes in the mechanisms of extrinsic and intrinsic control of vascular smooth muscle (VSM) reactivity, contractility and integrity that may be involved in the genesis of essential hypertension. VSM variables to be measured during suffusion of small mesenteric arteries and veins of the spontaneously hypertensive rat (SHR) and its normotensive WKY control include: in vivo transmembrane potentials and electrical activity; in vivo pressure, diameter and vessel tone; intracellular VSM Ca2 ion activity; frequency distribution of sympathetic efferent activity and plasma and small vessel norepinephrine and epinephrine concentrations. These variables will be measured comparatively in the two animal groups as a function of anesthesia, age, alpha and beta receptor blockade, electrogenic pump blockade, and sympathetic chemical denervation. It is anticipated that this data coupled with that already contributed by other investigators working in this research area will significantly advance our knowledge at the membrane level of the sequence of control mechanisms that gradually become abnormal in the increasingly complex loss of cardiovascular homeostasis underlying essential hypertension.